TY - JOUR
T1 - DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases
AU - BIOS Consortium
AU - Wielscher, Matthias
AU - Mandaviya, Pooja R.
AU - Kuehnel, Brigitte
AU - Joehanes, Roby
AU - Mustafa, Rima
AU - Robinson, Oliver
AU - Zhang, Yan
AU - Bodinier, Barbara
AU - Walton, Esther
AU - Mishra, Pashupati P.
AU - Schlosser, Pascal
AU - Wilson, Rory
AU - Tsai, Pei Chien
AU - Palaniswamy, Saranya
AU - Marioni, Riccardo E.
AU - Fiorito, Giovanni
AU - Cugliari, Giovanni
AU - Karhunen, Ville
AU - Ghanbari, Mohsen
AU - Psaty, Bruce M.
AU - Loh, Marie
AU - Bis, Joshua C.
AU - Lehne, Benjamin
AU - Sotoodehnia, Nona
AU - Deary, Ian J.
AU - Chadeau-Hyam, Marc
AU - Brody, Jennifer A.
AU - Cardona, Alexia
AU - Selvin, Elizabeth
AU - Smith, Alicia K.
AU - Miller, Andrew H.
AU - Torres, Mylin A.
AU - Marouli, Eirini
AU - Gào, Xin
AU - van Meurs, Joyce B.J.
AU - Graf-Schindler, Johanna
AU - Rathmann, Wolfgang
AU - Koenig, Wolfgang
AU - Peters, Annette
AU - Weninger, Wolfgang
AU - Farlik, Matthias
AU - Zhang, Tao
AU - Chen, Wei
AU - Xia, Yujing
AU - Teumer, Alexander
AU - Nauck, Matthias
AU - Grabe, Hans J.
AU - Doerr, Macus
AU - Lehtimäki, Terho
AU - Bell, Jordana T.
N1 - Funding Information:
H.J.G. has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier, and Janssen Cilag as well as research funding from Fresenius Medical Care. All other study authors declare no competing interests.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/5/3
Y1 - 2022/5/3
N2 - We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.
AB - We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.
UR - http://www.scopus.com/inward/record.url?scp=85129996814&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-29792-6
DO - 10.1038/s41467-022-29792-6
M3 - Article
C2 - 35504910
AN - SCOPUS:85129996814
SN - 2041-1723
VL - 13
SP - 2408
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2408
ER -
